Higher prostate cancer risk is well established in African Americans compared with Caucasian Americans, but little is known about factors contributing to this high risk. In our Tobago Prostate Survey, we have documented an extraordinarily high rate of prostate cancer, 16% among Tobago men aged 50-79, in the Afro-Caribbean population on the island of Tobago. We have discovered three risk domains which may contribute to the excess prostate cancer risk in this population: 1) indicators of high cumulative exposure to mitogenic factors (e.g., sex steroid hormones, growth factors) as assessed by bone mineral density; 2) host susceptibility (molecular variation in genes related to sex steroid hormone and interleukin 6 signaling); and 3) infection (most likely chronic) with human herpes virus 8 (HHV8). Moreover, our studies suggest biologically plausible interactions among these risk domains. Specific aims. 1. Continue screening to increase the case control series to 550 cases, 1100 non-cases. 2. To evaluate the association of molecular variation in major hormonal signaling genes and susceptibility to prostate cancer among Afro-Caribbean men. 3. To test the hypotheses that HHV8 exposure and molecular variation in the hormonal signaling genes are each independently related to prostate cancer risk, and test the hypothesis that interactions among these factors are a major determinant of risk. Data from other studies suggest that African Americans share the high risk sex hormone related genotypes observed in the Tobago population. HHV8 seropositivity is not rare in the US population. Confirmation of the association of HHV8 infection with prostate cancer risk, and further definition of sex hormone related genetic susceptibility, will identify a high risk group which may warrant development of interventions, such as hormone modulation, or HHV8 vaccine or anti-viral therapy, which could reduce risk for prostate cancer among Afro-Caribbeans, African Americans and other populations. [unreadable] [unreadable]